Designing Cardin-Motif Peptide and Heparin-Based Multicomponent Advanced Bioactive Hydrogel Scaffolds to Control Cellular Behavior

Recently, peptide and sugar-based multicomponent systems have gained much interest in attaining the sophisticated structure and biofunctional complexity of the extracellular matrix (ECM). To this direction, we have designed for the first time a biologically relevant minimalist Cardin-motif peptide capable of binding ECM-derived glycosaminoglycans. Herein, we explored Cardin-motif peptide and heparin-based biomolecular matrix by employing simple noncovalent interactions at the molecular level. Interestingly, this peptide was inadequate to induce hydrogelation at ambient pH due to the presence of basic amino acids. However, addition of heparin successfully triggered its gelation at physiological pH following favorable electrostatic interactions with heparin. Importantly, the newly developed scaffolds displayed tunable nanofibrous morphology and superior mechanical properties as controlled simply by the differential mixing ratio of both biomolecular entities. Additionally, these composite scaffolds could closely mimic the complexity of ECM as they demonstrated superior biocompatibility and enhanced growth and proliferation of neural cells as compared to the peptide scaffold.